Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection

Abstract

Objective - To test the life-sparing and therapeutic effect of a parenterally administered virus-specific antiviral phosphorodiamidate morpholino oligomer (PMO) for treating kittens during outbreaks of severe viral disease. Animals - 112 kittens of various sex and age in 4 trials involving 3 outbreaks of naturally developing caliciviral disease. Procedures - Each trial provided an opportunity to investigate the disease. A calicivirus isolated from the liver of a cat that died with hemorrhage and hepatitis was sequenced, and a PMO that had sequence specificity complementary to a 5′ region was synthesized. In vitro efficacy of the PMO was tested against the isolate, followed by 3 trials in outbreaks of severe caliciviral disease. The PMO was administered starting on day 1 of disease onset (0.7 to 5.0 mg/kg, SC, q 24 h) and continuing for up to 7 days. Survival time, clinical recovery, and caliciviral shedding were compared by use of various antiviral dosages. In a fourth trial involving nonfatal disease, a control treatment was administered for comparison. Results - In vitro blockage of caliciviral replication by the PMO was dose dependent. In trials 1 to 3 in which survival was the endpoint, 47 of 59 cats receiving PMO survived but only 3 of 31 survived without PMO treatment. Antiviral treatment reduced viral shedding and hastened clinical recovery, as measured by weight gains and clinical condition. Conclusions and Clinical Relevance - These data provided evidence that virus-specific PMOs were effective in treating kittens with severe Vesivirus disease and suggested a broader application for other viruses and species, including humans.